Cell Movements: From Molecules to Motility (book)

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Cell Movements: From Molecules to Motility (second edition) by Dennis Bray (google books entry) is a book I read because I thought I might do a PhD related to cell movement - more specifically, creating a computer modelling framework for movement. This summary is mostly a compilation of concepts from each chapter, plus a few extra interesting facts.

I thought this book was great - cell movement is really interesting, and this book was easy to understand. These notes are mostly for my own benefit, but no substitute for buying the book and seeing all the figures!


Chapter 1: Cell Swimming

  • Cells so small encounter different physical problems than say fish.
  • Progress is dominated by viscosity of environment; inertia is negligible.
  • Due to small size -> tiny Reynolds number -> cell don't need to be streamline -> don't create turbulence. Also cannot get anywhere via jet propulsion.
  • Cilia propel cells by viscous sheer - minimizing viscous resistance in recovery stroke.

  • Cells suspended in water undergo continual random motion due to thermal agitation -> Brownian motion. Their movements are dominated by viscosity and inertia has little influence.
  • Many types of free-living cells have evolved whiplike surface appendages known as flagella and cilia. These enable the cell to move/swim in a directed fashion through water.
  • Bacteria swim by flagella - stiff helical rods of protein that rotate by means of a motor embedded in the cell wall.
  • Eukaryotic flagella (eg: human sperm) are much larger and propagate bending waves along their length. They push or pull the cell along straight or gyrating paths.
  • Cilia are closely similar in design to eukaryotic flagella, but shorter and usually present in large numbers on surface of cells. Many protozoa swim through the coordinated beating of thousands of surface cilia.
  • Fields of cilia are also used by cell to circulate water over their surface. Sessile protozoa use cilia in this manner for feeding. Sheets of epithelial cells in higher animals often use cilia to direct the flow of mucous secretions in ducts and passages.
  • The basic design of eukaryotic cilia and flagella recurs in different forms specialized for particular tasks, including cell adhesion and sensory detection.

Chapter 2: Migrating of Cells over Surfaces

  • Viscous resistance increases enormously for a body moving close to a solid surface (equation ...).
  • Neutrophils (an abundant type of granular white blood cell that is highly destructive of micro-organisms) roam freely in circulation & tissue. They are directed to suitable location by chemical changes in endothelial cells forming wall of blood vessels ("call for help"). Neutrophils migrate to bacterial infection area at up to 30µm/min -> each cell engulfs/destroys many bacteria, before it itself dies -> large number of dead neutrophils in cavities excavated from inflamed tissues are expelled as pus or autolyzed and absorbed in surrounding tissue.
  • Fibroblasts are normally sedentary (moving only slightly) cells, but when tissue is damaged, become highly motile and travel to wounded area.
  • Myxobacteria are gliding bacteria that live in soil & feed on insoluble organic molecules. They show two distinct forms of gliding movement: moving as single cells or as a large swarm.

  • Many cells migrate over solid surfaces by crawling or gliding. This includes free-living organisms such as amoebae and diatoms (Any of various microscopic one-celled or colonial algae of the class Bacillariophyceae, having cell walls of silica consisting of two interlocking symmetrical valves.) as well as indiviudual cells in the body of a multicellular animal.
  • When a cell crawls or glides over a surface, its movements are dominated by viscous forces, as they are for swimming cells.
  • Large free-living amebae crawl by extending and retracting stubby pseudopodia. As they move, streams of cytoplasm move the fill the growing pseudopodia.
  • White blood cells move from the circulation and roam freely within the vertebrate body, searching for infections and decay.
  • Fibroblasts in connective tissue become actively motile during episodes of wound healing and tissue repair.
  • The developing embryo of most animal species is a site of continual widespread cell movement. Germ cells and precursors of nerve, muscle, and other tissues migrate to their correct locations.
  • Even cells in adult tissues such as liver, heart, or brain, can be stirred into independent movement by growing them in tissue culture.
  • Many tissue cells, such as fibroblasts, migrate over the surface of a culture dish by producing motile flattened lamellipodia (A sheet-like cytoplasmic extension produced by migrating polymorphonuclear white blood cells that permits movement along a substrate).
  • Specialized cells in many metazoa (A subdivision of the animal kingdom that includes all multicellular animal organisms having cells that are differentiated and form tissues and organs) also extend long thin filopodia that contribute to their migration.
  • Cell gliding is shown by myxobacteria, gregarines, diatoms and other organisms. Its mechanisms are poorly understood at present.
  • Some organisms employ modified cilia or flagella to crawl over surfaces rather than for swimming. Examples include swarming bacteria, hypotrichous protozoa, and heliozoans.

Chapter 3: Cell behavior

  • Repertoire of behaviors shown by single cells astonishingly rich and complex.
  • If swimming bacteria swims into region with greater dissolved attractants, tumbles are suppressed (duration of runs longer)... conversely, if concentration attractant less, tumble more frequent (runs shorter) -> thus travels towards attractant.
  • Two common terms:
    • Taxis; in which organism orients in direction of stimulus and moves towards it.
    • Kinesis, in which speed of movement changes with stimulus
  • Crawling cells are guided by terrain over which they move.

  • Physical and chemical factors in a cell's environment affect its otherwise random swimming or crawling, causing it to move in a specific direction.
  • Bacteria detect and swim toward distant sources of sugars, amino acids and other nutrient.*
  • Neutrophils are attracted by a variety of proteins, lipids and low-molecular-weight peptides that signal a bacterial infection or tissue destruction.
  • Many different cells show galvanotaxis - a directed response to an externally applied electrical field.
  • The physical terrain over which cells travel also influences their path. Crawling cells are responsive to subtle interactions with surface molecules, while swimming cells can avoid obstacles by having specific avoidance responses.
  • Collisions between migrating cells often generate specific responses, such as local paralysis of migration or the formation of cell aggregates. These may form the basis of complex social behavior as illustrated in the life cycle of the cellular slime molds.
  • Many single cells detect and respond to light, often avoiding very intense light of short wavelengths but being attracted by softer warmer lights. Interestingly, bacteria and algae use the same pigment molecule (rhodopsin) to detect light as we do in our eyes.
  • Single-celled amoebae and ciliates sometimes perform long, detailed sequences of actions in which they appear to make decisions and show motivation. Their behavior is controlled by protein-based biochemical circuits which serve a similar function to a nervous system in multicellular animals.

Chapter 4: The Cytoskeleton

  • Cytoskeleton contains:
    • Actin filaments: thin flexible filaments, diameter ~8nm made of protein actin - usually cross-linked into dense 3D weave or parallel bundles such as core of filopodia on cell surface.
    • Microtubules: long polymers of protein tubulin; relatively thick and inflexible - microtubule diameter ~15nm.
    • Intermediate filament: (common in animal cells) similar to microtubules, but smaller diameter ~10nm, filaments often radiate from protein matrix on nucleus to surrounding cytoplasm.
  • Typical cell in mammalian tissue might make over 10,000 different kinds of proteins.
  • Motile cell is "intelligent" -> frequently new & dangerous situations - cytoplasmic signalling systems and motile machinery is extensively interconnected (cross-talk exists at every level).

  • The structures that define cell shape and generate movement reside chiefly in an insoluble network of protein filament called the cytoskeleton.
  • In higher animals, cytoskeleton contains 3 principle types of filaments: actin filament, microtubules, and intermediate filaments, each with a distinctive protein composition and ultrastructure.
  • These filaments are linked to each other and to membranes by accessory proteins forming a three dimensional scaffolding that gives the cell its shape and capacity for movement.
  • The filaments forming the cytoskeleton are produced by polymerization reactions in which a single type of protein subunit adds repetitively. For acting filaments and microtubules, the process is coupled to nucleotide hydrolysis, thereby enabling the cell to control when, where and the extent to which it occurs.
  • The directed growth of a protein filament is a form of movement that can be harnessed by the cell. This was probably the basis of the earliest eukaryotic cell movements to appear during evolution.
  • However, the majority of known movements in present-day eukaryotic cells are driven by motor proteins that progress along either actin filaments or microtubules by undergoing cyclic ATP-driven changes in shape.
  • Different parts of the cytoskeleton are functionally connected to each other and to other components of the cell by protein links and by chemical signals carried by the changing concentrations of intracellular ions and small molecules.
  • The cytoskeleton is unique to eukaryotic cells and it plays a vital role in its most distinctive processes. The appearance of a dynamic cytoskeleton was probably one of the crucial steps in evolution of eukaryotic cells.
  • Cytoskeleton filaments almost always grow from pre-existing cellular structures. The cytoskeleton therefore carries information independently of the nucleus - this information being expressed in the position and structure of its components.

Chapter 5: Actin Filaments

  • Actin is abundant in all eukaryotic cells. Vertebrate species have a family of closely similar acting genes, expressed selectively in different tissues.
  • Actin exists as a monomer in a low-ionic-strength solution but spontaneously assembles into filaments on addition of salt.
  • Polymerization is regulated by ATP, which binds to (and stabilizes) acting monomers. Bound ATP is hydrolysed to ADP as polymerization proceeds.
  • The kinetics of polymerization reveals a simple mechanism of addition of monomers to filament ends, with the two ends of an actin filament growing at different rates.
  • Major shifts in actin polymerization occur during certain cell shape changes. There is evidence, from use of drugs such as cytochalasin, that growth and shrinkage of actin filaments occur continuously in the course of many movements.
  • Three types of protein control the pool of actin monomers in vertebrate cells. Thymosin sequesters (sequester - to cause to withdraw into seclusion. to remove or set apart; segregate) large quantities of actin in a reserve form; profiling suppresses unwanted nucleation and promotes filament growth at the barbed end; cofilin accelerates depolymerization at the pointed end.
  • In the cell, nucleating complexes of proteins determine where and when actin filaments form. Important clues to the identity of these proteins come from studies of pathogenic bacteria that commandeer the cell's actin machinery for their own infective cycle.
  • The length and number of actin filaments and their association with other components of the cell are controlled by a remarkably large collection of associated proteins, each of which binds to actin and influences its behavior in specific ways.
  • Many proteins are made by mRNA molecules targeted to actin filaments. These include actin itself and proteins responsible for cell polarity.

Chapter 6: Actin and Membranes

  • All animal cells possess a cortical layer of actin filaments on the inner face of the plasma membrane. This layer supports the flimsy lipid bilayer mechanically and is responsible for many cell surface movements.
  • The cortex is made of actin filaments attached at their barbed (plus) ends to the membrane and cross-linked into a three-dimensional web, or matrix, by proteins such as α-actinin and filamin.
  • Dynamic restructuring of the cortex occurs in response to calcium changes, mediated by severing proteins such as gelsolin.
  • Actin filaments are usually anchored to the plasma membrane by proteins with binding sites for both actin (or an actin-binding protein) and an integral membrane protein.
  • In the membrane skeleton of vertebrate red blood cells, short lengths of acting filament cross-linked by flexible spectrin molecules are attached to the plasma membrane by specific proteins such as ankyrin and band 4.1.
  • Adherens junctions between cells comprise clusters of molecules, which provide anchorage between one cell and the next, and bundles of actin filament attached to their cytoplasmic face.
  • Focal adhesion on the lower surface of cells in the culture form in response to extracellular matrix molecules such as fibronectin. Integrin molecules bind to matrix proteins on the outside of the cell and to talin, vinculin, α-actinin, and other proteins on the inside.
  • In addition to a simple anchoring function, adherens junctions and focal adhesions also have a signalling role and contain a number of protein kinases and their substrates.
  • Cortical actin also assembles in specific regions in response to external cues. Examples include the region of contact between a phagocytic cell and a suitable particle, where the accumulation of acting gives rise to pseudopodia that extend and engulf the particle.
  • Small G proteins, Rho, Rac, and Cdc42, have an important controlling influence over the association of acting with the plasma membrane, as in the formation of focal adhesions and filopodia.
  • Rapid formation and elongation of surface extensions occur in many cells in response to surface signals, for examples following fertilization of an egg or chemotactic stimulation of neutrophils or in the activation of blood platelets.
  • Actin filaments that form during these changes are assembled locally from actin monomers sequestered in the cytoplasm. Protein complexes near the membrane, formed in response to external cues, nucleate actin polymerization at specific locations.
  • Once formed, surface extensions can be stabilized by extensive cross-liking of their actin core and the linking of the latter to the plasma membrane, a well-characterized example being intestinal microvilli.
  • The packing of acting filaments in such stable extensions can be extremely regular. Hair cell stereocilia, present in amazingly precise arrays in the cochlea, illustrate the fine control a cell exerts over it cortical actin structures.

Chapter 7: Myosin

  • Myosins are a large family of motor proteins that produce movement along actin filaments.
  • Head regions of myosin molecules engage in an ATP-driven cycle in which they attach to an actin filament and pull against it, and then detach. Sophisticated motility assays, utilizing laser tweezers and other electronic devices, allow the interactions of individual molecules to be studied.
  • The rodlike tail region of the myosin II molecule allows it to aggregate into bipolar filaments with clusters of heads at either end. Interaction with actin filaments in antiparallel arrangements then leads to the shortening of the actin-myosin bundle.
  • Contractile bundles of actin filaments and myosin II are found widely in animals cells: in muscle, in stress fibres, in adhesion belts, and in the contractile ring formed during cell division.
  • Formation of contractive bundles is influenced by phosphorylation of myosin by specific kinases. These not only control assembly of myosin into filaments but also regulate myosin's actin-activated ATPase activity.
  • The assembly of contractile bundles relies on other proteins to hold the interacting actin and myosin in correct positions. The side-binding protein tropomyosin, in particular, often has a crucial influence on the type of bundle produced.
  • The contractile ring, by which large animal cells divide their cytoplasm, is a bundle of actin and myosin II filaments that forms and disperses during the cell cycle.
  • Genome analysis reveals that eukaryotic cells contain multiple different myosins. These all have head domains homologous to that of myosin II; their tail regions are highly divergent.
  • Genetic techniques indicate that myosins have many different functions in cells. These include the movement of vesicles to and from the plasma membrane, the transport of organelles, and the production and stabilization of pseudopods, microvilli, and stereocilia.

Chapter 8: Fibroblast Locomotion

  • Cell crawling much more difficult to study than flagellum, which can be studied in isolation.
  • Long way from a comprehensive picture.
  • Crawling cells extend blunt, stubby pseudopodia or fine filopodia, or may migrate by means of large flat lamellipodia flowing out in flat sheets in advance of the cell.
  • As (nematode) sperm crawls, meshwork of MSP filaments remains stationary with respect to substratum -> believed filaments assemble at leading margin of pseudopodium and disassemble at its base in continual tread milling motion.
  • A migrating fibroblast or keratocyte is typically wedge-shaped in outline, which a broad leading front and a narrow tail, or uropod. Uropod periodically snaps back into the cell as if elastic.
  • Front of migrating animal cell undergoes continual, local, expansion of its surface area as new filopodia or lamellipodia are added (each enclosed in a plasma membrane). Where does new membrane come from...? Recruited from neighbouring region of cell or created by insertion of components from cytoplasm - probably bit of both.

  • When an animal crawls over a surface it persons a repeated cycle of movement in which it (1) extends of the substratum, (2) forms an attachment to the surface, (3) pulls the remainder of the cell to the point of anchorage (contraction), and (4) detaches anchorage points at the rear of the cell.
  • Nematode sperm crawl by a variant of the normal process that does not require actin but does reveal the importance of assembly and disassembly of protein filaments.
  • The crawling of amoebae, which blood cells, and cells from skin and other tissues, is driven by a cortical layer of actin filaments in association with multiple other proteins.
  • Extension of the leading margin of the cell is caused by the polymerization of actin filaments. In lamellipodia, a branched network of actin filaments, growing at their barbed ends, pushes the plasma membrane forward.
  • Crucial factors in this leading edge extension are the Arp2/3 complex, gelsolin, and capping protein. At the base of the cortical actin meshwork, cofilin promotes the disassembly of filaments.
  • Transmembrane proteins (integrins) anchor the cell to its substratum by binding both to molecules of the extracellular matrix on the outside of the cell and to the actin cytoskeleton on the inside.
  • Cortical contractions due to myosin molecules pull structures towards the centre of the cell, causing the uropod to retract and unattached structures on the dorsal surface to move backward.
  • The cycle is complete by a forward movement of actin and other constituents through the cytoplasm to the leading margin of the cell.
  • In very large cells, such as Amoeba proteus, the forward extension of the pseudopodia is driven by streams of cytoplasm caused by the squeezing action of the cortex.
  • The direction taken by a migrating cell is responsible to both physical and chemical feature of its substratum. Cells can also respond to gradients of diffusing substances, as shown by the chemotaxis of Dictyostelium amoebae and neutrophils.
  • Cell locomotion is regulated by a web of reactions that convey signals from receptors in the plasma membrane to every part of the motile machinery. Key components in the regulatory network are calcium ions, inositol phospholipids, the Rho family of G proteins, and proteins related to WASP.

Chapter 9: The Molecular Basis or Muscle Contraction

  • Skeletal muscles are built up of long, thin fibers, each of which is a single, large multinucleated cell.
  • The cytoplasm of each muscle fibre is filled with myofibrils; the contractile unites of the muscle. These have regular striations along their length, indicative of a highly organized internal structure.
  • Myofibrils are stimulated to contract though a system of internal membranes that carry excitatory signals from the plasma membrane.
  • ATP is the immediate source of energy for contraction but is rapidly replenished, following hydrolysis, by a large reservoir of creatine phosphate.
  • Muscle contraction is produced by the sliding of acting filaments against myosin filaments.
  • The head regions of myosin molecules, projecting from myosin filaments, undergo and ATP-driven cycle in which they attach to adjacent actin filaments, undergo a change in shape that pulls one filament against the next, and then detach.
  • Two accessory proteins - troponin and tropomyosin - allow the contraction of skeletal muscle to be regulated by Ca2+. In the absence of calcium they bind to the actin filaments in such a way that they inhibit the binding of myosin heads.
  • Two extremely long stringlike molecules, titin and nebulin, act like molecular rulers for myofibril assembly, determining the precise length of actin and myosin filaments and their location in the sarcomere.

Chapter 10: Muscle Development

  • During embryonic development in vertebrate animals, mononucleate myoblast fuse into long myotubes and progressively differentiate into mature skeletal muscle fibers.
  • A population of myoblasts remain dormant in adult muscle but can be activated if the muscle is damaged, when they proliferate, fuse and form new fibers.
  • Myoblast fusion and muscle differentiation are under the control of a small number of master genes.
  • Myofibrils form by a regulated process in which thick and thin filaments assemble first and then are linked together. Titin plays a crucial role in this process, helping to form the Z-disc and acting as a template for thick filament assembly.
  • Microtubules have a role in early myoblast development serving to align myofibrils with the long axis of the cell.
  • Changes in myofibrillar structure and protein components can take place even in an adult muscle. Excercise, hormonal changes, and the pattern of electrical stimulation received from motor neutrons all activate different genes and modify the paths of mRNA maturation, leading to changes in the composition and structure of the microfibrils.

Chapter 11: Microtubules

  • Microtubules are stiff, hollow tubes built from tubulin dimers. They are polarized structures that grow faster at one end (the plus end) than at the other (minus) end.
  • Microtubule-organizing centres, such as centrosomes, protect the minus end of microtubules and nucleate new microtubules.
  • Slow growing microtubules are especially unstable and liable to rapid disassembly. They show a phenomenon called dynamic instability in which they alternate in stochastic fashion between periods of growth and periods of rapid shrinkage.
  • Dynamic instability can be increased, decreased, or even suppressed entirely by proteins that associate with the microtubules. For example, microtubules and effect that is regulated by phosphorylation.
  • Conversely, the fluctuating of a microtubule can be stabilized by protein complexes that capture the plus end - a process that helps specify the position of microtubules in a cell.

Chapter 12: Organelle Transport

  • Mitochondria, membrane vesicles, protein complexes, RNA molecules, and other organelles move continually from one location to another in the eukaryotic cytoplasm along tracks provided by microtubules.
  • By means of microtubules-based transports, cells establish and maintain regions of different function and are able to become large and asymmetric in shape.
  • Nerve axons have a particular acute dependence on organelle transport. Most protein synthesis occurs in the cell body and the products have to be transported over long distances (often many millimetres).
  • In nerve axons, microtubules are longitudinally aligned with their plus ends pointing away from the cell body. Microtubule associated proteins such as tau, bind along the length of microtubules, promoting their stability and increasing their mechanical stiffness.
  • Microtubules in dendrites are also arranged in parallel bundles, but in this case both polarities are present. Dendrites also have a distinct set of microtubules-associated proteins, including MAP2, and carry different organelles.
  • Movement away from the nerve cell body is driven by a family of kinesins. Most of these have two heads and a tail and move in a similar fashion to a conventional myosin, although with special features that adapt them to organelle transport.
  • A large superfamily of proteins related to kinesisn has been identified by recombinant DNA techniques. These have similar motor domains but differ markedly in their molecular anatomies and in their motile function in the cell.
  • Movement toward the cell body is driven by a microtubule motor called cytoplasmic dynein. This is a large protein related to the dynein found in eukaryotic cilia and flagella.
  • Attachment of cytoplasmic dynein to membrane cargoes occurs though a protein complex called dynactin. The dynein/dynactin complex drives many movements inside cells, including the movement of microtubules themselves.
  • Some membrane vesicles carry both kinesin and dynein, and perhaps also myosin molecules on their surface. Control of the direction of the organelles is then exerted by switching motors on and off at the appropriate time.
  • An enormous variety of cell movements, such as color changes in fish scales, diurnal changes in shape of retinal cells, tentacle feeding gin protozoa, and transport of ribosomes, nuclei, cytoskeleton filaments, and virus particles, depend on organelle transport. The molecular basis for most of these movements remains to be discovered.

Chapter 13: Mitosis

  • Bacteria divide by a simpler process than eukaryotic cells, but one of the proteins involved, FtsZ, is clearly related in structure to tubulin.
  • The eukaryotic cell cycle consists of several different phases. These include S phase during which the nuclear DNA is replicated and M phase during which the nucleus divides (mitosis) and then the cytoplasm divides (cytokinesis).
  • Events in the eukaryotic cell cycle are controlled by proteins called cyclins that rise and fall in amount at specific times. Cyclins activate protein kinases, called Cdk's which then phosphorylate and hance regulate multiple other target proteins.
  • The onset of M phase is signalled by the break-up of the nuclear membrane and formation of a mitotic spindle made of microtubules, which segregates chromosomes to opposite poles of the cell. In higher animals, the spindle forms on two centrosomes, which have duplicated and moved to opposite sides of the nucleus.
  • Upon dissolution of the nuclear envelope, microtubules of the spindle attach to chromosomes at discrete structures called kinetochores situated on either side of the chromosomal centromere.
  • Two sets of kinetochore-associated microtubules extending from the mitotic poles manoeuvre chromosomes to a position midway between two poles.
  • The movement of chromosomes by the spindle is driven both by microtubule motor proteins and by microtubule polymerization and depolymerization.
  • A control mechanism monitors the positioning of chromosomes on the midplane of the dividing cell, perhaps by a tension-dependent dephosphorylation, and generated a signal when all chromosomes have become suitably aligned.
  • The signal activates a complex of proteins called APC that initiates anaphase - the separation of chromosomes - by triggering a series of proteolytic events.
  • At anaphase, the tension in chromosomes is suddenly released as sister chromosomes detach from each other and are pulled to opposite poles. The two poles also move farther apart, possibly because of sliding forces developed between the parallel arrays of microtubules.
  • During the final phase of mitosis, telophase, the nuclear envelope reforms around each group of separated chromosomes and the mitotic spindle disassembles.
  • Similar arrays of microtubules to those found in mitosis are used during meiosis to segregate chromosomes into germ line cells, and during fertilization to facilitate the fusion of male and female pronuclei.

Chapter 14: Cilia

  • Cilia have a cylindrical core containing a ring of nine doublet microtubules. These cause the cilium to bend by sliding against each other.
  • Side-arms of the motor protein ciliary dynein extend from each microtubule doublet and make contact with the adjacent doublets.
  • Contact stimulates an ATPase in the dynein head and, as shown in cell-free motility assays, causes it to walk along the microtubule doublet towards its minus end.
  • Over 200 accessory proteins are associated with the flagellar axoneme. These form a variety of axoneme structure such as the dynein arms, the radial spokes, and nexin links that decorate the microtubules.
  • One of the protofilaments of the outer doublet microtubules is made not of tubulin but a fibrous protein, tektin, which is related in structure to intermediate filaments. Tektin might act as a molecular ruler to position other projections along the axoneme.
  • A central apparatus comprising a central pair of microtubules with attached structures runs down the middle of the axoneme. A series of radial spokes project from the central apparatus towards the inner dynein arms.
  • Both the frequency of the ciliary beat and, in some cases, its waveform can change in response to environmental influences. Changes are mediated by an increase or decrease in the concentration of second messengers, especially calcium ions and cAMP.
  • The often complex waveform of the ciliary beat results from a coordinated inhibitory control of dynein arms by the radial spokes. The spokes may modulate the activity of kinases and phosphates that act on dynein.
  • Axonemes vary widely in the sperm of different species and in modified cilia that act as sense organs in many animal species.
  • A human deficiency called Kartagener's syndrome, is caused by defects in ciliary axonemes. Patiens with this condition suffer from chronic bronchitis and immotile sperm.
  • Another function often associated with Kartagener's syndrome is an inversion of the left-right asymmetry of the body. Normal asymmetry has now been shown to arise from the asymmetric beating of cilia at an early stage of embryogenesis.
  • Even more divergent types of axoneme occur in the motile axostyles found in protozoa, often composed of thousands of parallel microtubules. The assembly of these structures depends on nucleating structures and specific cross-links.

Chapter 15: Centrioles and Basal Bodies

  • The length and number of flagella and cilia are inherited characteristics of a particular cell type. Flagella regrow to their original length following experimental removal, often in the absence of protein synthesis.
  • The site and orientation of cilia and flagella and their characteristic ninefold symmetry are determined by basal bodies. These are morphologically similar to centrioles, with a cylindrical array of nine triplet microtubules.
  • Most axonemal proteins assemble into large complexes at the base of a cilium and are then transported by kinesin molecules to the tip of the cilium, where they form dynein arms, radial spokes, or other structures.
  • Unused complexes are carried back to the base of the cilium by cytoplasmic dynein. The continual transport of subunits up and down the cilium permits not only growth but also turnover of axonemal components.
  • Basal bodies are associated with a number of cytoskeleton structures including various types of striated rootlet. These contain centrin, a protein that undergoes a calcium-induced change in conformation and serves to control the orientation of the flagella.
  • Each centriole has a unique polarity and when a daughter forms it is oriented at right angles to the mother. The pair of centrioles is typically embedded in a centrosome.
  • Mother and daughter centrioles are associated with different structure and perform different function in the cell. Whereas both are capable of nucleating microtubules, only a mother centriole appears able to maintain a stable radial array of microtubules.
  • Basal bodies in general arise from centrioles, which themselves usually form in close association with a parent centriole. However, many examples exist where centrioles appear in a cell that previously had none.
  • Basal bodies and centrioles do not contain appreciable amounts of coding DNA. These is very little evidence to support the idea these organelles arose during evolution from prokaryotic symbionts.

Chapter 16: Bacteria Movements

  • Flagellar motors with diameter < 50nm able to spin at more than 300 revolutions per second!
  • Is thought new flagellin molecules add to tip down by diffusing down hollow central -> the longer flagellar gets, the slower it grows, as expected of diffusion limited process.
  • Motor spins by gradient of protons moving across membrane, turning rotor, which contains helix - alternating lines of charge.
  • Increase in chemoattractants suppresses rotation in tumbling direction.
  • Cyanobacteria glide by secreting mucilage.

  • Bacteria such as Escherichia coli swim by means of flagella made of single helical tubes of the protein flagellin.
  • Each flagellum is attached though a flexible hook to a motor embedded in the bacterial membrane which is driven by a flux of hydrogen ions across the membrane.
  • Because each flagellum has a helical handedness (usually left-handed), rotation in only one direction allows smooth swimming. Transient reversal of the motor produces chaotic changes in direction known as tumbling.
  • Alternation between swimming and tumbling in the medium is influenced by the presence of chemo attractants and repellents in the medium and forms the basis of the chemotactic response.
  • Analysis of nonchemotactic mutants of E. coli shows that attractants activate one of five kinds of chemotactic receptor in the plasma membrane, either directly or as a complex with a transport protein in the periplasmic space.
  • Each receptor molecule is part of a complex of protein on the inner face of the plasma membrane that generates a diffusible protein, CheYp, at levels depending on the ligand-bound state of the receptor.
  • The same cascade of signals also trigger the slower adaptation of the response through the reversible methylation oft eh chemotactic receptors. Methylation alters the rate at which CheYp is produces and hance modulates swimming performance.
  • We probably understand the chemotaxis of E. coli in greater detail than any other form of cell movement, but many unsolved mysteries about its detailed performance remain.
  • Many commonly occurring species of bacteria use a chemotactic mechanism that is basically similar to that of E. coli, but with numerous subtle modifications.
  • Both in the laboratory and in natural environments, bacteria often accumulate into large colonies, such as biofilms. Their social behavior depends both on motility and on the ability of bacteria to communicate with each other.
  • Some species of bacteria use flagella in other ways. Proteus uses large number of flagella like oars to swarm over surfaces; the flagella of spirochetes are enclosed in a membrane, enabling these cells to screw their way through viscous media.
  • Species of cyanobacteria have been discovered that swim rapidly through sea water without flagella or other obvious surface appendage. The mechanism (and function) of this form of motility is currently a mystery.

Chapter 17: Intermediate Filaments

  • Intermediate filaments are tough, insoluble polymers about 10 nm in diameter found in the cells of most animal tissues, made from fibrous intermediate filament proteins.
  • There are many tissue-specific forms of intermediate filaments. Keratin filaments supply the cutaneous covering of the animal. Nuclear lamins provide a vital structural base for chromatin in the nucleus. Vimentin, desmin, and neurofilaments tailor the shapes and mechanical properties of particular cells.
  • The family of intermediate filament proteins has more than 50 distinct members, each with a central rod domain, of conserved amino acid sequence, flanked at both ends by non-α-helical domains. Dimeric subunits associate with one another in large overlapping arrays to form the intermediate filament.
  • In contrast to the subunits of actin filaments and microtubules, those of intermediate filaments are highly variable in size and amino acid sequence. Most of the variation occurs in the terminal domains, which project from the surface of the intermediate filament and contribute tissue-specific functions.
  • Assembly of intermediate filaments is regulated by phosphorylation of terminal domains. In some cases, such as lamins and vimentin, phosphorylation can lead to the disassembly of filaments once they have formed.
  • Proteins associated with intermediate filaments such as desmoplakin, filaggrin, plectin, and BPAG1 form links to other parts of the cytoskeleton, thereby creating an integrated system throughout the cytoplasm.
  • The primary function of intermediate filaments is to structure cytoplasm and to resists stresses externally applied to the cell. Mutations that weaken this structural framework increase the risk of cell rupture and cause a variety of human disorders.

Chapter 18: Cell Mechanics

  • Cell movements are driven by physical forces and governed by the mechanical properties of cell components, principally its cytoskeleton.
  • Actin filaments, intermediate filaments, and microtubules behave as flexible rods in solution, which an elasticity similar to that of hard plastic. Microtubules are the most rigid of the three, whereas intermediate filaments have the greatest tensile strength.
  • The use of protein filaments as stiffeners in the cell is made possible by their longitudinal associations into bundles, typically held together by protein cross-links.
  • The growth of protein filaments by polymerization can be harnessed to generate a force.
  • Protein filaments form extensive three-dimensional networks in aqueous solutions, with complex, viscoelastic properties. Cytoplasm is also viscoelastic, although its properties vary with the cell type and the region in the cell.
  • Filaments bundles and networks in the cell have the unique feature that they can develop force, due the toe presence of molecular motors. Contraction in animal cell is resisted by a framework of compressive elements, such as microtubules.
  • A variety of experimental approaches have been used to measure the mechanical properties of whole cells. These reveal not only the contractile nature of the cell surface but also a network of mechanical links throughout the cytoplasm.
  • Cytoplasm has an extremely complex structure characterized by a very high concentration of macromolecules and a three-dimensional network of protein molecules and membranes that restrict the diffusion of vesicles and macromolecular complexes, while permitting molecules smaller than 20 nm to diffuse freely.
  • The properties of cytoplasm reflect the high concentration of proteins it contains. A significant fraction of the water inside cells (~20%) is closely associated with the surfaces of proteins and has different properties from bulk water.
  • For plants, fungi, and bacteria, hydrostatic pressure developed within the cytoplasm due to osmotic movements is a major driving force for cell expansion. Animal cells develop smaller internal pressures, but these could be sufficient to drive membrane expansion.
  • Cell membranes also maintain a surface tension that, although smaller than forces developed by the cytoskeleton, has a controlling influence on cell processes such as endocytosis and exocytosis.
  • Living cells are continually exposed to mechanical forces and have evolved specific mechanisms to detect and accommodate to these forces. Mechanosensitive ion channels, for example, respond to the stress in the cell surface and, by their affect on the cytoskeleton, trigger changes in metabolism and cell shape.

Chapter 19: Cell Shape

  • Bacteria such as E. coli have rigid cell walls made of cross-linked peptide glycan that are designed to withstand very high internal pressure generated by osmosis.
  • Plant cells have thick, multilayered walls composed of cellulose microfibris and associated polysaccharides and formed into compact, boxlike shapes.
  • Cell shape can be influenced by nongenetic, mechanical, or steric factors imposed by the surroundings. Close-packing in two or three dimensions often leads to compact polyhedral forms governed by simple geometrical rules.
  • Cells in vertebrate tissue are highly diverse in their size and shape, often reflecting their particular function in the body. Cell shape itself can have a determining influence of function, as can be seen by forcing cells to adopt specific shapes in tissue culture.

Chapter 20: Cell Movement in Embryos

  • The response of a growth cone at any specific location of embryo will be highly individualistic, so that different growth cones moving over the same terrain can and do select different paths. Decision to take one or another path is achieved by complex molecular machinery built from cytoskeleton proteins and associated by signalling molecules.

  • The development of form in a multicellular animal occurs though the stereotyped sequences of simple cell movements and shape changes that depend on the cytoskeleton.
  • At the earliest stage, regional differences in the cytoplasm of the eggs of many species are established during oogenesis or in the course of fertilization.
  • An important mechanism in the establishment of regional cytoplasmic differences is the targeted delivery of mRNA molecules by means of motor proteins and their anchorage to site on the actin cytoskeleton.
  • Precisely oriented planes of cleavage then allocate these different regions of cytoplasm to specific daughter cells.
  • The pathways followed by growth cone depend on the receptors it carries on its surface and the complex network of biochemical and physical signals that pass from these recepts to the cytoskeleton.